Chris Tucker:
Welcome to the Arthroscopy Journal podcast. I'm Dr. Chris Tucker from the Walter Reed National Military Medical Center and the podcast founding editor. Today we're discussing the use of bioinductive implants for rotator cuff repairs. I'm joined today by Dr. Adnan Saithna, who is in private practice in Scottsdale, Arizona at AZBSC Orthopedics. Dr. Saithna is an orthopedic surgeon specializing in sports medicine. And amongst many other academic and professional endeavors, he's an Associate Editor for the Arthroscopy Journal. Dr. Saithna was the author of the editorial commentary titled Bioinductive Collagen Implants Reduce Rotator Cuff Tear, yet Cost-Effectiveness and Improvement in Clinical Outcomes Are Unclear, published in the June, 2024 issue of the Arthroscopy Journal. Adnan, congrats on your work and welcome to our podcast.
Adnan Saithna:
Hey Chris, thanks for having me. I really appreciate the invitation. I also appreciate the congratulations on my work, but actually I wanted to congratulate you. This podcast really continues to grow from strength to strength and I'm sure the visibility of author contributions provided by you and the podcast is one of the many factors that have favorably influenced the recent journal impact factors. For those of you who don't know, the impact factor for Arthroscopy Journal has recently exceeded that of AJSM for the first time ever. It's really a great achievement. So congrats to you, Chris, and the rest of the editorial team.
Chris Tucker:
Well, thanks Adnan. I've enjoyed getting to know you over the last couple of years working together on the editor panel for the journal, and I think the strength of our journal is just the strength of the members who contribute, all of our authors, the research that we get to sift through and especially the hard work that the Associate Editors like yourself and our Editor-in-Chief Jim Lubowitz put into getting the top-notch studies out there for folks to benefit from. So kudos to you for all the hard work you do on the review end and the editorial end. So to that end, discussing your editorial commentary, which I think is one of the real key valuable topics I always look through in every issue. I want to discuss the bioinductive collagen implants, but just before we jump into that topic, could you just give us a little background on yourself and your practice and your career?
Adnan Saithna:
Absolutely. Yeah, so as you can probably tell from my accent, I'm originally from the UK. I undertook my residency training there and I did two years of sports medicine fellowship training after that. One was at the Royal Orthopedic Hospital in England and the second was at the Pan Am Clinic in Winnipeg with Pete McDonald and the co-faculty there. I then went back to the UK where I was in practice for about five years until my wife got tired of the dreary English weather and the rain and she made me move back with her to the US in 2019. So I'm in private practice, so with locations in Scottsdale and central Phoenix, and I have several academic affiliations including the University of Arizona. I've been involved with Arthroscopy Journal since about 2017, and I became an Associate Editor in 2023. Outside of orthopedic surgery, my wife and I are certainly glad to be here in Arizona, although the high on Friday was 118 degrees. But apart from that, my wife spent 20 years building up her own business in property management here. We love the people, amazing wildlife, scenery, and the outdoors life the desert has to offer. From a professional perspective, it's also a great place to be. People love being active and a large proportion of my patients are older athletes, which lends itself nicely to this podcast focus on rotator cuff injuries.
Chris Tucker:
Yeah. It's always nice to hear about some of the personal side of each of the guests I have on the show, and we're lucky to have pulled you across the pond from England. Although, like you said, I think the jet stream carries a slightly different breeze to the UK than is running over Arizona these days. Let's get right into the use of collagen implants for cuff repairs. Starting with the big picture, could you just describe for us what the impact of rotator cuff tears and their subsequent repair is on the society as a whole, healthcare system and your individual patients?
Adnan Saithna:
Chris, as we all know, the big picture is that the societal impact of cuff tears is massive. The burden includes patient and healthcare cost, loss of wages or employment, cost of rehabilitation is just some of the examples. And there's obviously many complex different ways to quantify the problem. However, in the context of this particular podcast, a particular focus on retear rates, I think the best metric to use is really to understand the cost of failed surgery. So very helpfully, Young et al in JSES 2023 reported that the predicted two-year healthcare costs of failed arthroscopic cuff repairs performed in the US during 2022 is going to be in excess of $400 million. To make sure I explained that properly, what they looked at was cuff repairs performed during 2022 and what the predicted costs over the next two years were for those cuff repairs that failed, so in excess of $400 million. So that's obviously a huge problem and a major part of why we're discussing this topic today.
Chris Tucker:
It's interesting to me that, as you noted in your commentary, despite advances in surgical technology and the biomechanics of repair, the retail rates of rotator cuff repairs haven't really improved much since the 1980s. And as you said, this has a significant estimated healthcare cost for these failed cuff repairs. What exactly is going on here and what is the rate limiting step in making progress<
Adnan Saithna:
So far in our careers, Chris, we've both seen major improvements in the biomechanics of cuff repair. Examples include better anchor design, anchor pullout is really rare now. We have double row repairs, which whether you are kind of aligned with or not, we can tell from biomechanical studies that they improve footprint restoration, increased contact pressures for healing, improve stiffness and load to failure. And we have better, stronger, broader sutures or tapes and suture configurations that all improve the tendon suture interface. So you would expect with these technical and biomechanical improvements, we should see improved outcomes, but as we already mentioned from the literature, we don't see that. So regardless of how amazing we each think we are in our own practices, the overall literature doesn't reflect any significant improvements since the 1980s. Figure about improvements based on this meta-analysis from McElvany et al. is published in AJSM in 2015. They basically looked at the literature between 1980 and 2012 and they looked at improvements in PROMs and anatomical results, so whether the cast actually healed. So this is a really good study. What it means is that the lack of improvement in clinical outcomes is at odds with the observed advances in surgical technology. So it seems to me that it's logical to conclude that the weakest link here is not biomechanics, it's probably the biology.
Chris Tucker:
Yeah, I think that's quite insightful. Can you just describe for us the basics now, beginning with what exactly is a bioinductive collagen implant? I'm curious to hear your thoughts on what it is, but also how this product is regulated and are all implants created equal?
Adnan Saithna:
Well, the specific focus of our podcast is really my commentary on the randomized control study from Iban et al. And in that study they used one particular example of bioinductive collagen implants, and there's several, but the example that they used is the Regeneten patch. This typically comes in a medium or large size, and to give context to that, the large size is only 25 by 30 millimeters. It's made of highly purified bovine achilles tendon derived type one collagen. The idea behind it is that it induces the growth of new tendon like tissue and by thickening existing native tissue it reduces strain, provides an optimized environment for healing, and inhibits tear propagation. It also gradually absorbs within six months potentially leaving a layer of new tendon like tissue. I don't think all bioinductive collagen implants are created equal, but the important thing to note here is that that's just my opinion because comparative studies are lacking.
However, we can still draw some important comparisons. For example, they're clearly important distinctions between structural and non-structural implants. And Regeneten is non-structural, it's a thin patch and could easily be torn if it's not handled gently. There are of course other products on the market that also use bioinductive collagen principles, but for example, since I've mentioned Regeneten, I'm going to give some balance here and also mention that CONMED have a bioinductive collagen implant, which has bioresorbable PLLA in it to provide structural integrity and theoretically it provides that structural integrity for up to two years before resorbing. So for sure when you consider using any of these types of biologic augmentation, you need to think about what the advantages are from a biological perspective and also from a structural perspective. And again, to give equipoise to this, we should also look at some alternative biological options. And it's worth mentioning human dermal allograft.
It's not strictly bioinductive, but it does provide structural support and biology since in-growth, incorporation, and remodeling can occur. It's also fairly robust physically when you handle it. Anyone who's tried to pass sutures through one intraarticular knows that it's not necessarily that easy. That stiffness and thickness lends itself to providing a structural benefit, not just a biological one, and that extends a larger role. For example, not just in augmenting a cuff repair, but also in superior capsule reconstruction, bursal cranial resurfacing, biologic tube neuroplasty, which are not indications for biological only implants. There's other factors that we can look at if we want to decide whether there's important differences. And the other one is fixation methods. Again, Regeneten has some pros and cons, and I think the biggest pro is that it's technically a very, very easy procedure. Kudos to the engineers who designed it. The implant's simply deployed in the subacromial space after a bursectomy.
Once deployed, it's fixed in place by a medial resorbable, PLA staples, which are very easy to insert and laterally peak anchors. The entire process is quick and efficient. But the trade-off is is that the staples can sometimes cause a synovitis and perhaps even lead to stiffness related complications during the resorption process. In contrast, human dermal allograft can fix that with a variety of different techniques. But it typically, in my practice, includes the use of suture passes and hooks and maybe even all inside all suture tensionable devices, which might be more or equally time-consuming, but perhaps avoid some of the aforementioned issues.
Chris Tucker:
Yeah. That was a wonderful summary of the available options we have for biological augmentation. You mentioned retrieval studies in your commentary, meaning investigations into the histologic and biological response to rotator cuff repairs when performed with the use of these bioinductive implants. What have those studies shown us about what happens when these implants are used in cuff repairs and how does that information help us?
Adnan Saithna:
To answer your question, I think it's worth considering what happens from a time zero perspective. So after implantation, our scaffold gets saturated with blood and that leads to platelet degranulation on contact with the patch, and therefore as a result of that degranulation also the presence of growth factors. And that in turn leads to rapid ingrowth of new blood vessels and fibroblasts producing new tissue, which remodels according to whatever the environment is. It has the ability to integrate with native tendon and induce new tissue formation by around 12 weeks, and that new tissue integrates and remodels into the patient's own tissue and the implant is typically completely absorbed by six months. Several studies have shown that this results in improved tendon thickness and actually in their randomized controlled trial, Iban et al showed that the actual mean difference was less than one millimeter. So it's not clear how much thickening we need for it to be useful to transform clinical outcomes and reduce retear rates. So that's definitely an area of interest, but what we know is that finite element analysis have indicated that if you add two millimeters of tissue on the bursal side of an articular sided supraspinatus tear, then we can reduce the peak strain at the site of the tear by about 40%.
Chris Tucker:
Yeah. That's very interesting correlation between bench research and hopefully translation into clinical research and outcomes. What is the currently available data showing us with respect to the use of bioinductive collagen implants as far as their impact on things like surgical times, complication rates, you had mentioned the synovitis and stiffness earlier, retear rates which is obviously a big topic for our discussion, and then actual clinical outcomes for patients, as well as cost.
Adnan Saithna:
So let's start with retear rates first since a significantly reduced retear rate was the main finding of Iban's work, they looked at 124 patients with non-acute medium to large full thickness tears with fatty infiltration grade less than or equal to two. They prospectively randomized to either trans osseous equivalent cuff repair with or without bovine collagen implant. So the key finding was that the retail rate was only 8% in the augmented group compared to 25% in the isolated cuff repair group. And so what we've said about the societal cost of retail at the start of this podcast, that's obviously a really important finding. The authors didn't report any complications, but complications are certainly reported in the literature and I've observed them in my own clinical practice.
The literature shows that there's several case reports of synovitis and stiffness related issues. And I've personally observed synovitis in a very small proportion of my own patients, which thankfully has usually settled with a steroid injection. But have also had a couple of patients who needed reoperation, one for stiffness related complications. And then another, that implant seemed to dislodge and actually ended up I think becoming a loose body, which although the synovitis settled down I had to do a reoperation to remove that. Even though Iban didn't report any complications in their series, and it's a randomized controlled trial, we have to look at it from the perspective that they only had 124 patients, which is a small number to get a reliable estimate of the rate of complications.
So what we really need to understand is this is much bigger series with more data to determine the true re-operation rate and complication rate. With regards to the other part of your question about the impact on surgical times, so I can tell you that the procedure is pretty quick. Obviously surgical time has an impact on cost, so does implant pricing, the need for re-operation, success of surgery and improving prompts, for example, return to work as well. These are very complicated analysis, so they're difficult to interpret. But to my knowledge, there's two cost analysis performed and both of them are favorable for the use of bovine collagen implant over an isolated repair.
Chris Tucker:
All right. So taking the title of your commentary into consideration, just what are the concerns over the use of these bioinductive collagen implants for rotator cuff repairs with respect to both cost-effectiveness and impact on clinical outcomes?
Adnan Saithna:
That's a great question and I think it's really the crux of the matter. We know from Iban et al that the collagen implant is effective in reducing retail rates. And actually there's other studies that support that benefit including a more recent randomized control trial. But one of the issues with the work at hand is really that the number needed to treat was approaching six. That basically means that we need to treat six patients to avoid a single retear, but we all recognize that many patients with retears are asymptomatic or minimally symptomatic. So what I would really want to know is what's the number needed to treat to prevent symptomatic or clinically important retears. So in summary, I would worry that the RCT in question, are we really avoiding retears that might have been asymptomatic and that's reinforced by the fact that there was no difference in problems between their groups.
I think it's also important that we've got to consider that the manufacturers terminated early another international prospective multicenter randomized control trial that assessed large to massive tears. The clinical results are not yet published, but my understanding is that the reason for termination was not safety related, but due to lack of clinical efficacy. And perhaps that's due to the inclusion of massive tears, which we all know have less predictable outcomes after repair, but perhaps they're also the group that we need the most help with from a biological perspective. So on the basis of these considerations, my opinion is that the cost-effectiveness analysis that have been done have been under informed. It's also the case that they're both subject to industry involvement, whether that's through study sponsorship or author consultancy. And that's not a criticism, in fact, I want to thank industry for helping us to try to tackle this important societal problem, but I think we also need to evaluate studies with the appropriate context.
Chris Tucker:
Yeah. I think that's a wonderful analysis of both of those points, which like you said is really the crux of this topic. So transitioning to a more clinical setting rather than the investigational research that we've been talking about so far, how are you currently counseling your patients and advising them on your use or lack thereof of this type of an implant when it comes to performing rotator cuff repair surgery? Have you developed some sort of personal framework around which you built your own indications for offering and/or using them?
Adnan Saithna:
Absolutely. I think the first thing to say is that we've pointed out some of the limitations of the existing literature here in the podcast for the purposes of discussion, but there's also some important benefits as we mentioned reduced retear rate. But one of the other benefits that we haven't discussed yet is in the setting of partial tears. Typically we only operate on patients with partial tears once they've failed non-operative treatment because many of them do well with non-operative treatment. So I'm really talking here about the group that have failed non-operative treatment, and historically the options for them have been either tear completion and repair, which works great, but I think there must be some sense that if it fails, we as surgeons made that tear bigger. Or alternatively in situ repair, which seems appealing given that context, but is often associated with increased pain and stiffness in the first six months.
In fact, we've published a systematic review on that and it seems that at longer term follow-up that early increase in pain and stiffness compared to other tear types evens out. But that's not an easy process either for the surgeon or the patient if they're struggling with pain and stiffness in the early period. It's great to have an alternative solution, which is Regeneten, and I've enjoyed using that in my bioinductive collagen implants, which I've enjoyed using in my partial cuff tear patients. The huge advantages is is that the majority seem to firstly have rapid and impressive early pain relief compared to in situ repairs. I discontinued their sling by two weeks postoperatively, which is also quicker than a standard type repair. But on the downside, I have observed some complications. As I said, I had two cases of patients that needed reoperation in some cases of synovitis. So the number of overall complications I've seen, and overwhelmingly I feel that this is a good alternative treatment option to the historical options that we've pointed out some flaws about.
But in terms of my individual framework, in order to reduce the risk of some of these issues, I prefer to avoid using in anyone who has significant preoperative stiffness and also in patients where the pain is higher than we might typically expect for the pathology. I think that these patients have an element of capsulitis and that's why they're so painful. But probably put some at higher risk of complications in terms of stiffness and early postoperative pain. I want patients to be able to easily move their arm and regain full range of motion by around two or three weeks postoperatively. I also use bioinductive collagen implants to augment full thickness tears if I think the patients are at high risk typically on the revision setting. But based on this more recent literature, it seems that there is a role with broader applicability too.
Chris Tucker:
Yeah. I think listening to your thoughts on a lot of these subtopics related to the bioinductive implant, I think we can logically deduce where I think the next steps in research have to be, but I just wanted to hear your thoughts on where you think we need to go as a profession from here with respect to further investigation of these implants.
Adnan Saithna:
There's lots of directions we can go here, but for me, one of the biggest limitations of the existing work is, again, that we didn't observe an important difference in patient reported outcome measures. That makes me concerned that we might be by using these types of implants, be avoiding retears that were not going to be symptomatic anyway, at least in the short term. And that makes it very difficult to reliably determine cost-effectiveness. Again, we need to remember that an RCT was stopped probably for lack of efficacy. So I think some of the different directions we can go in are firstly related to the use of this issue in the fact that we didn't identify a significant difference in PROMs. In my editorial, I alluded to the fact that the authors had used the MCID in their study to evaluate between group differences in PROMs. And although the MCID has been popularized over the last 10 years, I think we really want to try and move away from it, or at least from a sole reliance on it at this time.
The MCID was originally introduced by Jaeschke in 1989 to determine the clinical relevance of specific treatments, and he defined it at that time in a way that we don't really use academic work. So he defined it as the smallest difference in score in the domain of interest which patients perceive as beneficial, and which would mandate in the absence troublesome side effects and excessive cost, a change in the patient's management plan. And so that latter part of this statement is often emitted in contemporary descriptions of MCID and instead it's more typically stated just as I think the authors did in this study, as the minimum improvement that translates into a patient perceived change in their health status. However, without the latter part of the statement, the MCID loses much of its value and doesn't accurately represent what Jaeschke set out to determine, which is a level of clinical importance sufficient to change management.
Another way to, I guess that was a wordy explanation. So in order to illustrate in a different way, I'd say to you, Chris, if I told you you needed to have your cuff repaired next week and be in a sling for the next four to six weeks and then undergo months of PT, I'm sure you're going to be pretty unhappy about that. But you would be even more unhappy if at the end of all that time, financial investment that all you gained was a minimal clinical improvement. So why should we use the MCID as a metric. As Jim Lubowitz and others stated in their editorial in 2022, MCID is a low bar, patients aren't interested in that and neither should we be.
What we want to know is about more significant measures or not more significant, more clinically meaningful to the patient, important differences. So that would be things like substantial clinical benefit, patient acceptable symptom state, and maximum outcome improvement. Those are a whole different topic, but I would point listeners in the direction of Jim's editorial or the editorial commentary that Mark Co and I published earlier this year that provides more insight on those directions. But in simple terms, we need to analyze clinically meaningful differences to understand the efficacy of procedures and inform sample size. And I think that's a very important point for future randomized control studies. We need to get this right to know that the differences we're seeing are actually impactful for patients.
Chris Tucker:
Yeah. I think the nuances that you just highlighted is really the value, I think, in having an experienced associate editor who's insightful like yourself, and able to articulate some of those research focused measures and kind of translating into what matters clinically. So I really appreciate those thoughts and your comments there, and that was one of the main takeaways I took from your editorial commentary, so I'm glad you spoke to it.
Adnan, you provided us some really wonderful and informative insights on the current state of the use of bioinductive collagen implants for rotator cuff repairs, how they might be a potential game changer but also outlining the reasons why we just aren't quite there yet. Did you have any other closing remarks before we close out?
Adnan Saithna:
The only closing remark I have is that I really want to congratulate the authors of the original article. It's really fantastic to have authors submitting such high quality manuscripts that really advance our knowledge to Arthroscopy Journal. It's a great study, and although we've dissected out some of the pitfalls in this podcast, we should also highlight the strengths of it being a really well-designed RCT. So kudos to Iban and co-authors.
Chris Tucker:
Yeah, that's wonderful. So Adnan, once again, congrats on all your work. Thanks for sharing your time and your thoughts with us today.
Adnan Saithna:
Yeah. Thanks for having me, Chris. I've really enjoyed discussing this topic with you, and congratulations again on making this such an incredible podcast series.
Chris Tucker:
Dr. Saithna's editorial commentary titled Bioinductive Collagen Implants Reduce Rotator Cuff Retear, yet Cost-Effectiveness and Improvement in Clinical Outcomes Are Unclear, is published in the June, 2024 issue of the Arthroscopy Journal, which is available online at www.arthroscopyjournal.org.
This concludes this edition of the Arthroscopy Journal podcast.
The views expressed in this podcast do not necessarily represent the views of the Arthroscopy Association or the Arthroscopy Journal.
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